HIV Lipodystrophy 

HIV Lipodystrophy – 7 Interesting Facts

1. HIV-associated lipodystrophy is a clinical syndrome characterized by either peripheral fat loss (lipoatrophy), fat accumulation (lipohypertrophy), or a mixture of these features, often with abnormalities in glucose and lipid metabolism, among PWH (people with HIV infection) treated with ART (antiretroviral therapy)
2. Diagnosis of HIV-associated lipodystrophy is primarily made by patient’s self-report and physical examination findings
3. HIV-associated lipodystrophy has both psychological and metabolic complications that may affect ART adherence and increase the risk of cardiovascular disease among PWH
4. Thymidine analogues, such as stavudine and zidovudine, are the main drivers of lipoatrophy among PWH; there is no clear association between one specific ART agent or class and lipohypertrophy
5. Switching from thymidine analogues to alternative NRTIs (nucleoside reverse transcriptase inhibitors), such as abacavir and tenofovir, can partially reverse peripheral lipoatrophy¹³¹⁴
6. Additional research is needed to understand the effects of newer ART agents, such as INSTIs (integrase strand transfer inhibitors) and tenofovir alafenamide, on weight gain and fat distribution
7. New therapies for the treatment of HIV-associated lipodystrophy that are safe and effective, with lasting improvement in fat distribution, are needed

Introduction

• HIV-associated lipodystrophy is a disorder of either fat loss (lipoatrophy), fat accumulation (lipohypertrophy), or both, with or without abnormalities in lipid and glucose metabolism, among PWH (people with HIV infection) receiving ART (antiretroviral therapy)
  • Lipoatrophy is defined by a loss of subcutaneous fat most apparent in peripheral sites, such as the face, limbs, and buttocks, but also in central sites, such as the abdomen
  • Lipohypertrophy is defined by an accumulation of fat in the dorsocervical region (“buffalo hump”), abdomen (visceral fat), or breast tissue
  • Mixed presentation of peripheral lipoatrophy and visceral fat accumulation (lipohypertrophy) may be seen
  • Metabolic abnormalities in PWH receiving ART are characterized by insulin resistance and dyslipidemia

Epidemiology

• Historical prevalence estimates vary widely from 10% to 80% among PWH, due to heterogenous definitions of HIV-associated lipodystrophy used in early studies, host and viral factors, and ART use and duration of treatment¹
• Prevalence in the era of more modern ART regimens is uncertain

Etiology and Risk Factors

Etiology

• Lipoatrophy
  • Pathogenesis is thought to be due to mitochondrial toxicity and inhibition of mitochondrial DNA polymerase gamma by thymidine analogues (eg, stavudine, zidovudine)²
• Lipohypertrophy
  • Although ART use has been associated with fat accumulation, no single agent or class is thought to be causative
• Metabolic abnormalities
  • Dysregulation of adipocytokines, such as adiponectin, leptin, and resistin, seen in PWH with lipoatrophy and lipohypertrophy may explain increased risk of insulin resistance³⁴⁵⁶

Risk Factors

• Lipoatrophy
  • Exposure to NRTIs (nucleoside reverse transcriptase inhibitors)
    • Use of the thymidine analogues, stavudine and, to a lesser extent, zidovudine, is the main risk factor associated with HIV-associated lipoatrophy⁷⁸
  • Exposure to other ART classes
    • First-generation protease inhibitors, such as indinavir, may act synergistically with NRTIs to increase the risk of lipoatrophy, but discontinuation of protease inhibitors is not associated with improvement in lipoatrophy⁹
  • Host factors
    • Increased age may be associated with increased risk of lipoatrophy¹⁰
    • Mitochondrial DNA haplogroups and hemochromatosis gene polymorphisms may modify lipoatrophy risk¹¹
  • Viral factors may be associated with increased risk of lipoatrophy
    • High baseline viral load before ART initiation
    • Lower CD4 cell count before ART initiation
• Lipohypertrophy
  • Host factors
    • Increased age
    • White race
    • Higher baseline fat content
    • Lower CD4 cell count at ART initiation (less than 200 cells/µL)¹²¹³
  • Recent research suggests there may be increased risk of weight gain with use of newer ART agents, such as the INSTIs (integrase strand transfer inhibitors) (eg, dolutegravir, bictegravir)¹⁴¹⁵¹⁶
    • However, it is not clear if this is due to central fat accumulation (visceral adiposity) or generalized weight gain (proportional increases in both subcutaneous and visceral fat) and whether the NRTI tenofovir alafenamide may contribute to the risk of weight gain seen with INSTIs

Diagnosis

Approach to Diagnosis

• Lipodystrophy is largely a clinical diagnosis based on patient-reported changes in fat distribution and objective physical examination findings
  • Anthropometric measurements, such as weight, BMI, waist circumference, waist to hip ratio, and triceps skinfold measurement, are mainly used in research settings and are not superior to patient’s self-report or physical examination findings¹⁷
  • Radiographic measurements of fat depots using DXA, CT, and MRI scans are limited to use in research settings due to cost or third-party payer coverage, expert interpretation, and no well-established reference ranges¹⁸

Workup

History

• Take a thorough history, including a medication history
  • History of exposure to NRTIs of the thymidine analogue class, such as stavudine and zidovudine, may support a diagnosis of lipoatrophy

Physical Examination

• Lipoatrophy
  • A loss of facial fat (buccal and temporal fat pads), prominent nasolabial folds, periorbital hollowing, and/or prominent facial musculature may suggest facial lipoatrophy
  • A loss of fat in arms and legs and/or prominent veins and musculature in the limbs may suggest peripheral lipoatrophy
  • A loss of “pinchable” subcutaneous fat around the abdomen (may not be clinically apparent in persons with abdominal lipohypertrophy) may suggest abdominal lipoatrophy
• Lipohypertrophy
  • A dorsocervical fat pad (“buffalo hump”) may suggest lipohypertrophy
  • Breast hypertrophy (fatty enlargement of the breast tissue) may also be seen in lipohypertrophy
  • An increase in abdominal circumference due to visceral adipose tissue accumulation may suggest lip hypertrophy
    • Waist to hip ratio greater than 0.95 in males and greater than 0.85 in females, or abdominal circumference greater than 102 cm in males and greater than 88 cm in females is considered an objective measure of increased abdominal circumference¹⁹
    • Increased waist circumference with stable weight and BMI or minimal “pinchable” abdominal fat is suggestive of central lipohypertrophy with concomitant central lipoatrophy (loss of subcutaneous abdominal fat)
    • HIV-associated fat accumulation may be distinguished from simple obesity, which is defined by an increase in both visceral and subcutaneous adipose tissue, whereas HIV-associated fat accumulation is not associated with increased subcutaneous abdominal adipose tissue
  • Lipomas (subcutaneous fat nodules) may develop because of lipohypertrophy

Laboratory Tests

• No specific laboratory tests are necessary for diagnosis of lipoatrophy nor lipohypertrophy
• Metabolic abnormalities
  • Obtain laboratory studies to assess for impaired glucose tolerance or insulin resistance
    • Fasting blood glucose²⁰²¹
    • Oral glucose tolerance test²⁰²¹
    • Glycated hemoglobin A1c²⁰²¹
  • Obtain laboratory studies to assess for dyslipidemia
    • Fasting lipid panel (total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride levels)²²²³

Differential Diagnosis

• Differential diagnosis for HIV-associated lipodystrophy (Table 1) includes:
  • AIDS wasting syndrome
  • Cushing syndrome
  • Simple obesity

Table 1. Differential Diagnosis: HIV-associated lipodystrophy.

Condition	Description	Differentiated by
AIDS wasting syndrome	Involuntary weight loss in patients with advanced HIV infection, not on effective ART, defined by loss in both lean muscle mass and adipose tissue2425	In HIV-associated lipoatrophy, patients are on ART (primarily stavudine and to a lesser degree zidovudine) and have no reduction in lean muscle mass262728
Cushing syndrome	Syndrome of excess glucocorticoid exposure, which may result in obesity, dorsocervical fat pad, and impaired glucose tolerance29	In HIV-associated lipohypertrophy (fat accumulation), there is an absence of hypercortisolism3031
Simple obesity	Excess weight characterized by an increase in both visceral and subcutaneous adipose tissue32	HIV-associated lipohypertrophy is not associated with increased subcutaneous abdominal adipose tissue2633

Caption: ART, antiretroviral therapy.

Data from many references.24252627282930313233

Treatment

Approach to Treatment

• Treatment of HIV-associated lipodystrophy and associated metabolic abnormalities should be considered in all persons with this condition

Nondrug and Supportive Care

• Lifestyle modification
  • Review diet and exercise
    • Decreased caloric intake and increased physical activity may decrease visceral fat accumulation in patients with lipohypertrophy, though data are limited³⁴
    • Dyslipidemia and insulin resistance seen in some persons with HIV-associated lipodystrophy may increase atherosclerotic cardiovascular disease risk³⁵³⁶³⁷
• Clinicians should be aware that HIV-associated lipodystrophy may cause psychological stress, such as low self-esteem and stigma, associated with HIV infection and treatment
• In addition, lipodystrophy has been shown to be an independent risk factor for ART nonadherence

Drug Therapy

• Lipoatrophy
  • Avoid thymidine analogue use
    • Lipoatrophy may be prevented by avoiding thymidine analogue use²⁸³⁸
    • This class of NRTI is not recommended for use in modern HIV treatment guidelines³⁹
  • Change in NRTI
    • Switch patients from stavudine or zidovudine to an alternate NRTI, such as abacavir or tenofovir disoproxil fumarate
      • Shown to increase peripheral limb fat, partially reversing peripheral lipoatrophy³⁸⁴⁰
      • Strongly consider in the rare patients who remain on stavudine or zidovudine⁷²⁸⁴¹
      • Switch studies referenced above were conducted before the availability of tenofovir alafenamide, which is generally the preferred formulation of tenofovir, though this formulation is also associated with overall weight gain
      • Review prior HIV resistance patterns before ART switch to minimize risk of virologic failure³⁹
  • Thiazolidinediones
    • Thiazolidinediones drugs are peroxisome proliferator–activated receptor gamma agonists that improve insulin sensitivity and promote adipocyte differentiation in vitro
    • Consider in PWH with lipoatrophy and impaired glucose tolerance⁴²
    • Pioglitazone 30 mg daily may modestly increase peripheral limb fat at 48 weeks compared with placebo among people with self-reported HIV-associated peripheral lipoatrophy not receiving stavudine⁴²
      • Adverse effects
        • Hepatotoxicity
          • Monitor liver enzymes every 3 to 6 months
        • Bladder cancer in patients with diabetes
        • Fluid retention
        • Congestive heart failure
          • Avoid in persons with symptomatic heart failure
        • Decreased bone mineral density
• Lipohypertrophy
  • Metformin
    • An oral biguanide that lowers blood glucose levels by inhibiting hepatic glucose production
    • Consider metformin 500 mg twice daily in persons with HIV-associated fat accumulation and comorbid impaired glucose tolerance
    • Will reduce both visceral and subcutaneous adipose tissue, so must use with caution in persons with mixed lipoatrophy and lipohypertrophy⁴³
    • Adverse effects
      • Gastrointestinal distress
      • Diarrhea
      • Lactic acidosis
  • Tesamorelin
    • Growth hormone–releasing hormone analogue that stimulates pituitary gland growth hormone secretion to induce hepatic synthesis of IGF-1 (insulinlike growth factor 1)
    • Found to have a modest effect on decreasing visceral adipose tissue and improved self-reported body satisfaction scores compared with placebo; no effect on subcutaneous adipose tissue⁴⁴
    • Tesamorelin 2 mg given by daily subcutaneous injection;⁴⁵ visceral fat will reaccumulate after discontinuation of therapy⁴⁴
    • Adverse effects
      • Theoretical increased risk of malignancy⁴⁶
      • Elevated IGF-1 levels⁴⁶
        • Monitor IGF-1 levels every 6 months
        • Consider dose reduction or discontinuation of therapy if levels rise above the general reference range⁴⁶
      • Glucose intolerance
        • Monitor hemoglobin A1c levels every 3 months⁴⁵
  • Glucagonlike peptide 1 receptor agonists
    • Emerging data suggest total body fat and visceral adipose tissue may be reduced with weekly injection of semaglutide 1 mg weekly at 32 weeks but also with reduction in peripheral limb fat (may worsen lipoatrophy) and lean body mass⁴⁷
• Metabolic abnormalities
  • Management of HIV-associated metabolic abnormalities, such as dyslipidemia and impaired glucose tolerance, is similar to the management of these conditions in the general population
    • Statin therapy has been shown to reduce the risk of major cardiovascular events among PWH with low to moderate cardiovascular disease risk who do not meet criteria for statin therapy for the general population⁴⁸
    • Moderate-intensity statin should be considered for all PWH aged 40 to 75 years³⁹
    • Drug-drug interactions between statins and ART (especially boosted regimens containing ritonavir or cobicistat) should be reviewed; statin dose reduction may be needed³⁹
    • Statins may cause muscle toxicity ranging from myalgias to myonecrosis and rhabdomyolysis, though muscle-related adverse events were extremely rare in both the statin and placebo arms of the REPRIEVE trial (Randomized Trial to Prevent Vascular Events in HIV)⁴⁸
      • Monitor for muscle-related symptoms after initiation of statins
  • No change in ART has shown clearly defined improvement in metabolic profiles among patients with lipohypertrophy
• New therapies for the treatment of HIV-associated lipodystrophy that are safe and effective, with lasting improvement in fat distribution, are needed

Treatment Procedures

• Lipoatrophy
  • Temporary fillers are the preferred treatment for facial lipoatrophy
    • Polylactic-L-acid injection⁴⁹
      • Biodegradable tissue expander that promotes collagen formation
      • Well tolerated and durable for more than 1 year from last injection
      • Expense may be cost prohibitive
    • Calcium hydroxylapatite injection⁵⁰
      • Hydroxylapatite microspheres serve as collagen scaffolding
      • Well tolerated and durable for more than 18 months from last injection
      • Expense may be cost prohibitive
  • Permanent fillers
    • Synthetic materials injected into vacant fat pockets and do not dissolve⁵¹
      • Polyacrylamide
      • Polymethylmethacrylate
    • Lipoatrophy may improve with time after a change in ART, and permanent fillers may cause disfigurement with such changes
    • These materials are not FDA approved
    • Concern for injection site infections with use
  • Fat autotransplant⁵²
    • Transfer of patient’s fat deposits from buttock or abdomen to other sites affected by lipoatrophy
    • Limited fat depots due to lipoatrophy at abdominal and buttock sites may limit feasibility
• Lipohypertrophy
  • Surgical intervention
    • Liposuction (suction-assisted lipectomy) may be beneficial for dorsocervical fat pad⁵³⁵⁴
    • Reduction mammoplasty may also be considered⁵³
    • Cannot be employed for visceral adipose tissue accumulation
    • Associated with high cost
    • Risks include surgical complications, such as bleeding, infection, and the potential for fat reaccumulation⁵⁵

Follow-Up

Monitoring

• Routine monitoring of weight, BMI, waist circumference, patient-reported changes in fat distribution, and visual inspection for clinical features of HIV-associated lipodystrophy is recommended at regular clinic visits
• Routine monitoring of fasting lipids and glucose levels recommended per HIV primary care treatment guidelines; no additional monitoring is advised for persons with HIV-associated lipodystrophy

Complications

• HIV-associated lipodystrophy is associated with an increased risk of diabetes and dyslipidemia, which may increase the risk of atherosclerotic cardiovascular disease
• Morphological changes associated with both lipoatrophy and lipohypertrophy may cause psychological stress that impairs ART adherence

Prognosis

• Switching patients off of thymidine analogues remains the single most important change that can prevent further lipoatrophy and modestly reverse the fat loss in PWH, though this class of drugs is rarely used today^28385657
• Temporary facial fillers are efficacious but may not be affordable for many patients
• Tesamorelin may reduce visceral abdominal fat, but rebound occurs, if it is stopped¹⁷

Screening and Prevention

Prevention

• Lipoatrophy may be prevented by avoiding thymidine analogue use
• There is no specific method for prevention of lipohypertrophy, because no single antiretroviral agent or class has been identified as a major risk factor

Author Affiliations

Yotam Arens, MD
Medicine
Infectious Diseases
Weill Cornell Medical College

Marshall J. Glesby, MD, PhD
Medicine
Infectious Diseases
Weill Cornell Medical College

References

1.Heath KV et al. Lipodystrophy-associated morphological, cholesterol and triglyceride abnormalities in a population-based HIV/AIDS treatment database. AIDS. January 26, 2001;15(2):231-239.

View In Article|Cross Reference

2.Hammond E et al. Human immunodeficiency virus treatment-induced adipose tissue pathology and lipoatrophy: prevalence and metabolic consequences. Clin Infect Dis. September 1, 2010;51(5):591-599.

View In Article|Cross Reference

3.Ranade K et al. Genetic analysis implicates resistin in HIV lipodystrophy. AIDS. August 20, 2008;22(13):1561-1568.

View In Article|Cross Reference

4.Sweeney LL et al. The role of adipokines in relation to HIV lipodystrophy. AIDS. May 11, 2007;21(8):895-904.

View In Article|Cross Reference

5.Nagy GS et al. Human immunodeficiency virus type 1-related lipoatrophy and lipohypertrophy are associated with serum concentrations of leptin. Clin Infect Dis. March 15, 2003;36(6):795-802.

View In Article|Cross Reference

6.Kubota N et al. Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem. July 19, 2002;277(29):25863-25866.

View In Article|Cross Reference

7.Gallant JE et al. Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. N Engl J Med. January 19, 2006;354(3):251-260.

View In Article|Cross Reference

8.Dubé MP et al. Long-term body fat outcomes in antiretroviral-naive participants randomized to nelfinavir or efavirenz or both plus dual nucleosides. Dual X-ray absorptiometry results from A5005s, a substudy of Adult Clinical Trials Group 384. J Acquir Immune Defic Syndr. August 15, 2007;45(5):508-514.

View In Article|Cross Reference

9.Martínez E et al. Impact of switching from human immunodeficiency virus type 1 protease inhibitors to efavirenz in successfully treated adults with lipodystrophy. Clin Infect Dis. November 2000;31(5):1266-1273.

View In Article|Cross Reference

10.Jacobson DL et al. Prevalence of, evolution of, and risk factors for fat atrophy and fat deposition in a cohort of HIV-infected men and women. Clin Infect Dis. June 15, 2005;40(12):1837-1845.

View In Article|Cross Reference

11.Hulgan T et al. Hemochromatosis gene polymorphisms, mitochondrial haplogroups, and peripheral lipoatrophy during antiretroviral therapy. J Infect Dis. March 15, 2008;197(6):858-866.

View In Article|Cross Reference

12.Lichtenstein KA et al. Incidence of and risk factors for lipoatrophy (abnormal fat loss) in ambulatory HIV-1-infected patients. J Acquir Immune Defic Syndr. January 1, 2003;32(1):48-56.

View In Article|Cross Reference

13.McDermott AY et al. CD4+ cell count, viral load, and highly active antiretroviral therapy use are independent predictors of body composition alterations in HIV-infected adults: a longitudinal study. Clin Infect Dis. December 1, 2005;41(11):1662-1670.

View In Article|Cross Reference

14.Sax PE et al. Weight gain following initiation of antiretroviral therapy: risk factors in randomized comparative clinical trials. Clin Infect Dis. September 12, 2020;71(6):1379-1389.

View In Article|Cross Reference

15.McComsey GA et al. Body composition changes after initiation of raltegravir or protease inhibitors: ACTG A5260s. Clin Infect Dis. April 1, 2016;62(7):853-862.

View In Article|Cross Reference

16.Eckard AR et al. Weight gain and integrase inhibitors. Curr Opin Infect Dis. February 2020;33(1):10-19.

View In Article|Cross Reference

17.Wohl DA et al. Current concepts in the diagnosis and management of metabolic complications of HIV infection and its therapy. Clin Infect Dis. September 1, 2006;43(5):645-653.

View In Article|Cross Reference

18.Brown TT et al. Management of the metabolic effects of HIV and HIV drugs. Nat Rev Endocrinol. September 20, 2011;8(1):11-21.

View In Article|Cross Reference

19.Lean ME et al. Waist circumference as a measure for indicating need for weight management. BMJ. July 15, 1995;311(6998):158-161.

View In Article|Cross Reference

20.Freitas P et al. Lipodystrophy defined by fat mass ratio in HIV-infected patients is associated with a high prevalence of glucose disturbances and insulin resistance. BMC Infect Dis. August 6, 2012;12:180.

View In Article|Cross Reference

21.Meininger G et al. Body-composition measurements as predictors of glucose and insulin abnormalities in HIV-positive men. Am J Clin Nutr. August 2002;76(2):460-465.

View In Article|Cross Reference

22.Wohl D et al. The associations of regional adipose tissue with lipid and lipoprotein levels in HIV-infected men. J Acquir Immune Defic Syndr. May 1, 2008;48(1):44-52.

View In Article|Cross Reference

23.Currier J et al. Regional adipose tissue and lipid and lipoprotein levels in HIV-infected women. J Acquir Immune Defic Syndr. May 1, 2008;48(1):35-43.

View In Article|Cross Reference

24.Mulligan K et al. Altered fat distribution in HIV-positive men on nucleoside analog reverse transcriptase inhibitor therapy. J Acquir Immune Defic Syndr. April 15, 2001;26(5):443-448.

View In Article|Cross Reference

25.Polsky B et al. HIV-associated wasting in the HAART era: guidelines for assessment, diagnosis, and treatment. AIDS Patient Care STDS. August 2001;15(8):411-423.

View In Article|Cross Reference

26.Bacchetti P et al. Fat distribution in men with HIV infection. J Acquir Immune Defic Syndr. October 1, 2005;40(2):121-131.

View In Article|Cross Reference

27.Mallon PW et al. HIV-associated lipodystrophy: description, pathogenesis, and molecular pathways. Curr Diab Rep. April 2002;2(2):116-124.

View In Article|Cross Reference

28.Carr A et al. Abacavir substitution for nucleoside analogs in patients with HIV lipoatrophy: a randomized trial. JAMA. July 10, 2002;288(2):207-215.

View In Article|Cross Reference

29.Nieman LK et al. The diagnosis of Cushing’s syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. May 2008;93(5):1526-1540.

View In Article|Cross Reference

30.Lo JC et al. “Buffalo hump” in men with HIV-1 infection. Lancet. March 21, 1998;351(9106):867-870.

View In Article|Cross Reference

31.Roth VR et al. Development of cervical fat pads following therapy with human immunodeficiency virus type 1 protease inhibitors. Clin Infect Dis. July 1998;27(1):65-67.

View In Article|Cross Reference

32.Ibrahim MM. Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev. January 2010;11(1):11-18.

View In Article|Cross Reference

33.Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM). Fat distribution in women with HIV infection. J Acquir Immune Defic Syndr. August 15, 2006;42(5):562-571.

View In Article|Cross Reference

34.Thöni GJ et al. Reduction of fat accumulation and lipid disorders by individualized light aerobic training in human immunodeficiency virus infected patients with lipodystrophy and/or dyslipidemia. Diabetes Metab. November 2002;28(5):397-404.

View In Article|Cross Reference

35.Glesby MJ et al. Abdominal fat depots and subclinical carotid artery atherosclerosis in women with and without HIV infection. J Acquir Immune Defic Syndr. March 1, 2018;77(3):308-316.

View In Article|Cross Reference

36.Palella FJ et al. Anatomic fat depots and coronary plaque among human immunodeficiency virus-infected and uninfected men in the multicenter AIDS cohort study. Open Forum Infect Dis. April 2016;3(2):ofw098.

View In Article|Cross Reference

37.Hadigan C et al. Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy. Clin Infect Dis. January 2001;32(1):130-139.

View In Article|Cross Reference

38.Martin A et al. Reversibility of lipoatrophy in HIV-infected patients 2 years after switching from a thymidine analogue to abacavir: the MITOX Extension Study. AIDS. April 30, 2004;18(7):1029-1036.

View In Article|Cross Reference

39.US Department of Health and Human Services. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. ClinicalInfo.HIV.gov. Accessed April 17, 2024.

View In Article|Cross Reference

40.McComsey GA et al. Improvement in lipoatrophy associated with highly active antiretroviral therapy in human immunodeficiency virus-infected patients switched from stavudine to abacavir or zidovudine: the results of the TARHEEL study. Clin Infect Dis. January 15, 2004;38(2):263-270.

View In Article|Cross Reference

41.Gallant JE et al. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA. July 14, 2004;292(2):191-201.

View In Article|Cross Reference

42.Slama L et al. Effect of pioglitazone on HIV-1-related lipodystrophy: a randomized double-blind placebo-controlled trial (ANRS 113). Antivir Ther. 2008;13(1):67-76.

View In Article|Cross Reference

43.Hadigan C et al. Metformin in the treatment of HIV lipodystrophy syndrome: a randomized controlled trial. JAMA. July 26, 2000;284(4):472-477.

View In Article|Cross Reference

44.Falutz J et al. Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data. J Clin Endocrinol Metab. September 2010;95(9):4291-4304.

View In Article|Cross Reference

45.Egrifta (tesamorelin). Package insert. EMD Soreno Inc; 2010.

View In Article

46.Renehan AG et al. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet. April 24, 2004;363(9418):1346-1353.

View In Article|Cross Reference

47.McComsey GA et al. 1984. Effects of semaglutide on adipose tissue in HIV-associated lipohypertrophy. Open Forum Infect Dis. 2023;10(suppl 2):ofad500.111.

View In Article|Cross Reference

48.Grinspoon SK et al. Pitavastatin to prevent cardiovascular disease in HIV infection. N Engl J Med. August 24, 2023;389(8):687-699.

View In Article|Cross Reference

49.Levy RM et al. Treatment of HIV lipoatrophy and lipoatrophy of aging with poly-L-lactic acid: a prospective 3-year follow-up study. J Am Acad Dermatol. December 2008;59(6):923-933.

View In Article|Cross Reference

50.Silvers SL et al. Prospective, open-label, 18-month trial of calcium hydroxylapatite (Radiesse) for facial soft-tissue augmentation in patients with human immunodeficiency virus-associated lipoatrophy: one-year durability. Plast Reconstr Surg. September 2006;118(3 suppl):34S-45S.

View In Article|Cross Reference

51.Sutinen J. Interventions for managing antiretroviral therapy-associated lipoatrophy. Curr Opin Infect Dis. February 2005;18(1):25-33.

View In Article|Cross Reference

52.Shuck J et al. Autologous fat grafting and injectable dermal fillers for human immunodeficiency virus-associated facial lipodystrophy: a comparison of safety, efficacy, and long-term treatment outcomes. Plast Reconstr Surg. March 2013;131(3):499-506.

View In Article|Cross Reference

53.Moyle GJ. Plastic surgical approaches for HIV-associated lipoatrophy. Curr HIV/AIDS Rep. August 2005;2(3):127-131.

View In Article|Cross Reference

54.Piliero PJ et al. Use of ultrasonography-assisted liposuction for the treatment of human immunodeficiency virus-associated enlargement of the dorsocervical fat pad. Clin Infect Dis. November 15, 2003;37(10):1374-1377.

View In Article|Cross Reference

55.Barton N et al. Excisional lipectomy versus liposuction in HIV-associated lipodystrophy. Arch Plast Surg. November 2021;48(6):685-690.

View In Article|Cross Reference

56.John M et al. Randomized, controlled, 48-week study of switching stavudine and/or protease inhibitors to combivir/abacavir to prevent or reverse lipoatrophy in HIV-infected patients. J Acquir Immune Defic Syndr. May 1, 2003;33(1):29-33.

View In Article|Cross Reference

57.Taramasso L et al. The switch from tenofovir disoproxil fumarate to tenofovir alafenamide determines weight gain in patients on rilpivirine-based regimen. AIDS. May 1, 2020;34(6):877-881.

View In Article|Cross Reference